Table 1 Synthesis of thiacalix[4]crowns 2a–f by use of an intermediate 3
R–X–R 5 (mol equiv.)
Base (mol equiv.)
Solvent
Yield (%)a of 4
Yield (%)b of 2
TsOCH2CH2OTsc 5a (3.0)
Cs2CO3 (3.0)
Cs2CO3 (3.0)
Cs2CO3 (3.0)
Cs2CO3 (3.0)
Cs2CO3 (3.0)
NEt3 (4.0)
THF–DMF (1 : 1)
DMF
THF
THF
THF–DMF (1 : 1)
THF
89 (4a)
71 (4b)
84 (4c)
75 (4d)
57 (4e)
50d (4f )
91 (2a)
99 (2b)
96 (2c)
96 (2d)
92 (2e)
96 (2f )
TsOCH2CH2OCH2CH2OTs 5b (1.2)
TsOCH2(CH2OCH2)2CH2OTs 5c (1.2)
TsOCH2(CH2OCH2)3CH2OTs 5d (1.2)
BrCH2(CH2)6CH2Br 5e (1.2)
ClCO(CH2)6COCl 5f (1.2)
a Isolated yield based on 3. b Isolated yield based on 4. c TS = toluene-p-sulfonate. d Calculated from 1H NMR of the reaction mixture.
Isopropylmethyl protons of 3 appear at 0.80, 1.15, 1.18, and
1.38 ppm as four sets of doublet (each 6H) indicating that the
rotation around the bonds between the Si and Pri groups is
restricted by steric hindrance.9 It has been shown previously
that 27,28-O-dialkylation products of 3 were in the 1,2-
alternate conformation as evidenced by an upfield shift of the
isopropylmethyl proton signals to 0.47, 0.80, 1.03, and 1.09
ppm due to the anisotropic shielding effect of the aryl rings at
the 27,28-positions. Thus, the upfield shift of the isopropyl-
methyl protons up to ca. 0.4 ppm should make a good probe for
judging the 1,2-alternate conformation of a disiloxane-capped
thiacalix[4]crown 4.
dried over anhydrous MgSO4. After filtration, the solvent was
removed in vacuo to obtain a crude product, which was purified
by column chromatography (silica gel, AcOEt–n-hexane =
1 : 10) to give 4c in 84% yield (0.45 g).
To a solution of 4c (0.32 g, 0.30 mmol) in THF (15 ml) was
added a 1.0 M solution of tetrabutylammonium fluoride in
THF (0.30 ml, 0.30 mmol) at room temperature. After stirring
for 1 hour, the mixture was cooled to 0 ЊC, diluted with 2 M
HCl, and extracted with chloroform. The organic layer was
washed with water and dried over anhydrous MgSO4. After
filtration, the solvent was removed in vacuo to obtain a crude
product, which was purified by column chromatography (silica
gel, AcOEt–n-hexane = 1 : 3) to give 2c in 96% yield (0.24 g).
1
For 4b–d, the H NMR signals of the most shielded iso-
propylmethyl protons appeared at 0.33–0.45 ppm, suggesting
that these compounds also should be in the 1,2-alternate con-
formation. It is interesting that the H NMR spectrum of 4a
1
Acknowledgements
showed no isopropylmethyl protons shifted upfield to the 0.4
ppm region. However, its bridging ethylene protons connected
to the 27,28-phenolic oxygens appeared at 1.60–3.95 ppm,
significantly shifted upfield as compared with (4.55–4.75 ppm)
of the product (2a) obtained after desilylation. Similarly, the
methylene protons of 4b–d connected to the 27,28-phenoxy
oxygens appeared at ca. 2.5 ppm, which were shifted to ca. 4.5
ppm region after desilylation to 2b–d (vide infra). These results
strongly suggest that the methylene protons of 4a–d connected
to the 27,28-phenoxy oxygens are subjected to the shielding
effect of the aryl rings at the 25,26-positions, which, in turn,
substantiates that all 4a–d take 1,2-alternate conformation. It
may be concluded that the single ethylene bridge of 4a pulls the
27,28-phenoxy oxygens inwardly to push the phenoxy nuclei at
the 27- and 28-positions away from the calix ring, thus reducing
the shielding effect on the disiloxane moiety.
The reaction of 3 with alkyl dihalide 5e or diacid dichloride
5f instead of oligo(ethylene glycol) bistoluene-p-sulfonates
could also be carried out smoothly to give 25,26-27,28-doubly
bridged compounds 4e,f in good yields, the conformations of
which were assigned also as 1,2-alternate based on the 1H NMR
criteria of the isopropylmethyl protons as stated above.
Deprotection of 4a–f was easily carried out by simply treat-
ing with tetrabutylammonium fluoride in THF to liberate the
proximal 25,26-bridged thiacalix[4]crowns and their analogues
2a–f quantitatively (Scheme 1, Table 1). 1H NMR signals for the
ArOCH2 moiety of these thiacalix[4]crowns appeared at 4.0–
5.0 ppm, in sharp contrast to those of 4a–d that appeared at
2.0–3.8 ppm. These results show that the ArOCH2 protons of
2a–d are free from the shielding effect of the 27,28-aryl rings,
which, in turn, suggests that these 25,26-calix[4]crowns are in
the cone conformation in CDCl3 at ambient temperature.
This work was supported by a Grant-in-Aid for Scientific
Research on Priority Area (No. 14044009) from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
References
1 (a) C. D. Gutsche, Calixarenes Revisited, Monographs in Supra-
molecular Chemistry, J. F. Stoddart, ed. The Royal Society,
Cambridge, 1998, vol. 6; (b) Z. Asfari, V. Böhmer, J. Harrowfield and
J. Vicens, Calixarenes 2001, Kluwer Academic, Dordrecht, 2001.
2 F. Vögtle, Supramolecular Chemistry: An Introduction, J. Wiley,
New York, 1991.
3 (a) Y. Kubo, S. Maeda, S. Tokita and M. Kubo, Nature, 1996,
382, 522; (b) Q. Y. Zheng, C. F. Chen and Z. T. Huang, Tetrahedron,
1997, 53, 10345; (c) F. Arnaud-Neu, S. Caccamese, S. Fuangswasdi,
S. Pappalardo, M. F. Parisi, A. Petringa and G. Principato, J. Org.
Chem., 1997, 62, 8041.
4 (a) R. Ungaro, A. Casnati, F. Ugozzoli, A. Pochini, J.-F. Dozol,
C. Hill and H. Rouquette, Angew. Chem., Int. Ed. Engl., 1994, 33,
1506; (b) Z. Asfari, C. Bressot, J. Vicens, C. Hill, J. F. Dozol,
H. Rouquette, S. Eymard, V. Lamare and B. Tournois, Anal. Chem.,
1995, 67, 3133; (c) V. Lamare, J. F. Dozol, S. Fuangswasdi,
F. Arnaud-Neu, P. Thuéry, M. Nierlich, Z. Asfari and J. Vicens,
J. Chem. Soc., Perkin Trans. 2, 1999, 271; (d ) J. S. Kim, J. H. Pang,
I. Y. Yu, W. K. Lee, I. H. Suh, J. K. Kim, M. H. Cho, E. T. Kim and
D. Y. Ra, J. Chem. Soc., Perkin Trans. 2, 1999, 837.
5 (a) H. Kumagai, M. Hasegawa, S. Miyanari, Y. Sugawa, Y. Sato,
T. Hori, S. Ueda, H. Kamiyama and S. Miyano, Tetrahedron Lett.,
1997, 38, 3971; (b) N. Iki, C. Kabuto, T. Fukushima, H. Kumagai,
H. Takeya, S. Miyanari, T. Miyashi and S. Miyano, Tetrahedron,
2000, 56, 1437; (c) N. Iki and S. Miyano, J. Inclusion Phenom.
Macrocyclic Chem., 2001, 41, 99.
6 (a) N. Iki, N. Morohashi, F. Narumi and S. Miyano, Bull. Chem. Soc.
Jpn., 1998, 71, 1597; (b) N. Morohashi, N. Iki, A. Sugawara and
S. Miyano, Tetrahedron, 2001, 57, 5557; (c) A. Bilyk, A. K. Hall,
J. M. Harrowfield, M. W. Hosseini, B. W. Skelton and A. H. White,
Inorg. Chem., 2001, 40, 672; (d ) A. Bilyk, A. K. Hall, J. M.
Harrowfield, M. W. Hosseini, G. Mislin, B. W. Skelton, C. Taylor and
A. H. White, Eur. J. Inorg. Chem., 2000, 823.
Experimental
The synthesis of 2,8,14,20-tetrathia-25,26-calix[4]crown-4 (2c)
via 27,28-O-disiloxanediyl-bridged 2,8,14,20-tetrathia-25,26-
calix[4]crown-4 (4c)
7 V. Lamare, J. F. Dozol, P. Thuéry, M. Nierlich, Z. Asfari and J. Vicens,
J. Chem. Soc., Perkin Trans. 2, 2001, 1920.
8 (a) H. Yamamoto, T. Sasaki and S. Shinkai, Chem. Lett., 1994,
469; (b) A. Arduini, W. M. McGregor, D. Paganuzzi, A. Pochini,
A. Secchi, F. Ugozzoli and R. Ungaro, J. Chem. Soc., Perkin Trans. 2,
1996, 839; (c) A. Arduini, L. Domiano, A. Pochini, A. Secchi,
R. Ungaro, F. Ugozzoli, O. Struck, W. Veboom and D. N. Reinhoudt,
Tetrahedron, 1997, 53, 3767.
To a solution of 3 (0.48 g, 0.50 mmol) in anhydrous THF
(50 ml) were added caesium carbonate (0.49 g, 1.5 mmol) and
tri(ethylene glycol) bistoluene-p-sulfonate 5c (0.28 g, 0.60
mmol). After heating at reflux with stirring for 30 hours, the
mixture was cooled to 0 ЊC, diluted with 2 M HCl, and
extracted with chloroform. The organic layer was washed and
9 F. Narumi, N. Morohashi, N. Matsumura, N. Iki, H. Kameyama and
S. Miyano, Tetrahedron Lett., 2002, 43, 621.
1844
J. Chem. Soc., Perkin Trans. 1, 2002, 1843–1844